Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation

Anna Caliò, John Eble, Ondrej Hes, Guido Martignoni, Saul E. Harari, Sean R. Williamson, Matteo Brunelli, Adeboye O. Osunkoya, Lisha Wang, Eva Comperat, Antonio Lopez-Beltran, Mingsheng Wang, Shaobo Zhang, Kendra L. Curless, Kristin M. Post, Hsim Yee Chang, Claudio Luchini, Lee Ann Baldrige, Gregory T. MacLennan, Rodolfo MontironiDavid Grignon, Liang Cheng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16INK4 and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85%) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16INK4 expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.

Original languageEnglish (US)
Pages (from-to)54096-54105
Number of pages10
JournalOncotarget
Volume8
Issue number33
DOIs
StatePublished - 2017

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Adenoma
Mutation
Wilms Tumor
Mutant Proteins
Immunohistochemistry
Monoclonal Antibodies
Staining and Labeling
Sensitivity and Specificity
Polymerase Chain Reaction

Keywords

  • BRAF
  • Immunohistochemistry
  • Kidney
  • Metanephric adenoma
  • Nephroblastoma/Wilms tumor

ASJC Scopus subject areas

  • Oncology

Cite this

Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation. / Caliò, Anna; Eble, John; Hes, Ondrej; Martignoni, Guido; Harari, Saul E.; Williamson, Sean R.; Brunelli, Matteo; Osunkoya, Adeboye O.; Wang, Lisha; Comperat, Eva; Lopez-Beltran, Antonio; Wang, Mingsheng; Zhang, Shaobo; Curless, Kendra L.; Post, Kristin M.; Chang, Hsim Yee; Luchini, Claudio; Baldrige, Lee Ann; MacLennan, Gregory T.; Montironi, Rodolfo; Grignon, David; Cheng, Liang.

In: Oncotarget, Vol. 8, No. 33, 2017, p. 54096-54105.

Research output: Contribution to journalArticle

Caliò, A, Eble, J, Hes, O, Martignoni, G, Harari, SE, Williamson, SR, Brunelli, M, Osunkoya, AO, Wang, L, Comperat, E, Lopez-Beltran, A, Wang, M, Zhang, S, Curless, KL, Post, KM, Chang, HY, Luchini, C, Baldrige, LA, MacLennan, GT, Montironi, R, Grignon, D & Cheng, L 2017, 'Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation', Oncotarget, vol. 8, no. 33, pp. 54096-54105. https://doi.org/10.18632/oncotarget.11117
Caliò, Anna ; Eble, John ; Hes, Ondrej ; Martignoni, Guido ; Harari, Saul E. ; Williamson, Sean R. ; Brunelli, Matteo ; Osunkoya, Adeboye O. ; Wang, Lisha ; Comperat, Eva ; Lopez-Beltran, Antonio ; Wang, Mingsheng ; Zhang, Shaobo ; Curless, Kendra L. ; Post, Kristin M. ; Chang, Hsim Yee ; Luchini, Claudio ; Baldrige, Lee Ann ; MacLennan, Gregory T. ; Montironi, Rodolfo ; Grignon, David ; Cheng, Liang. / Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation. In: Oncotarget. 2017 ; Vol. 8, No. 33. pp. 54096-54105.
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abstract = "BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16INK4 and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85{\%}) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80{\%}, specificity 100{\%}); in all cases we detected p16INK4 expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20{\%}) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.",
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AU - Harari, Saul E.

AU - Williamson, Sean R.

AU - Brunelli, Matteo

AU - Osunkoya, Adeboye O.

AU - Wang, Lisha

AU - Comperat, Eva

AU - Lopez-Beltran, Antonio

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AU - Luchini, Claudio

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AU - Cheng, Liang

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